Commercially available glow discharge mass spectrometry (GDMS) and high performance secondary ion mass spectrometry (SIMS) instrumentation will be evaluated for quantitative trace element analysis of very small biological samples. Sub-milligram or microliter quantities of bovine serum, bovine and rice flour, certified by the National Bureau of Standards, will be analyzed for the elements Na, K, Ca, Mn, Fe, Co, Cu, Zn and Se among others as a means of simulating small quantities of typical biological unknowns. Quantitation studies will be performed using internal standard, standard additions and isotope dilution methods to assess accurate and precision as a function of sample size and analytical protocol. There are many potential health-related applications for quantitative micro-trace element analysis in neonatology, nutrition studies, opthamology, toxicology and basic physiological research. Conventional techniques such as optical emission or absorption spectroscopy or electron microprobe analysis are inadequate for these problems. GDMS and high performance SIMS are ideal candidate technologies because of their very low gram-detectabilities (greater than 1 pg and less than 1 fg, respectively). Substantial modifications to existing instrumentation or procedures (Phase II) most likely will be required to achieve quantitative trace element analysis in micro- specimens comparable to conventional analysis of larger samples.